Accelerator-Based Production of Scandium Radioisotopes for Applications in Prostate Cancer: Toward Building a Pipeline for Rapid Development of Novel Theranostics.

In the field of nuclear medicine, the ß+ -emitting 43Sc and ß- -emitting 47Sc are promising candidates in cancer diagnosis and targeted radionuclide therapy (TRT) due to their favorable decay schema and shared pharmacokinetics as a true theranostic pair. Additionally, scandium is a group-3 transition metal (like 177Lu) and exhibits affinity for DOTA-based chelators, which have been studied in depth, making the barrier to implementation lower for 43/47Sc than for other proposed true theranostics. Before 43/47Sc can see widespread pre-clinical evaluation, however, an accessible production methodology must be established and each isotope's radiolabeling and animal imaging capabilities studied with a widely utilized tracer. As such, a simple means of converting an 18 MeV biomedical cyclotron to support solid targets and produce 43Sc via the 42Ca(d,n)43Sc reaction has been devised, exhibiting reasonable yields. The NatTi(γ,p)47Sc reaction is also investigated along with the successful implementation of chemical separation and purification methods for 43/47Sc. The conjugation of 43/47Sc with PSMA-617 at specific activities of up to 8.94 MBq/nmol and the subsequent imaging of LNCaP-ENZaR tumor xenografts in mouse models with both 43/47Sc-PSMA-617 are also presented.

Photonuclear production of 47Ca for 47Ca/47Sc generator from natural CaCO3 targets.

This work investigated the indirect production of 47Sc from natural Ca targets via 48Ca(γ,n)47Ca→47Sc + ß- + ν‾e with incident electron energies of 30, 35, and 40 MeV. The 47Ca production yields were simulated using the PHITS Monte Carlo simulation code and compared to experimental data. The simulated production rates for all three irradiations are in good agreement with experimental data within uncertainties. As a demonstration of the 47Ca/47Sc generator system, one of the irradiated CaCO3 targets was dissolved in nitric acid, and 47Sc was isolated from the target material using commercially available Eichrom DGA resin. The 47Sc was allowed to grow in, and the purification process was repeated with promising 47Sc and Ca recovery yields.

Imaging and dosimetric characteristics of 67 Cu.

In recent years the use of beta-emitting radiopharmaceuticals for cancer therapy has expanded rapidly following development of therapeutics for neuroendocrine tumors, prostate cancer, and other oncologic malignancies. One emerging beta-emitting radioisotope of interest for therapy is 67Cu (t1/2: 2.6 d) due to its chemical equivalency with the widely-established positron-emitting isotope 64Cu (t1/2: 12.7 h). In this work we evaluate both the imaging and dosimetric characteristics of 67Cu, as well as producing the first report of SPECT/CT imaging using 67Cu. To this end, 67Cu was produced by photon-induced reactions on isotopically-enriched 68Zn at the Low-Energy Accelerator Facility (LEAF) of Argonne National Laboratory, followed by bulk separation of metallic 68Zn by sublimation and radiochemical purification by column chromatography. Gamma spectrometry was performed by efficiency-calibrated high-purity germanium (HPGe) analysis to verify absolute activity calibration and establish radionuclidic purity. Absolute activity measurements corroborated manufacturer-recommended dose-calibrator settings and no radionuclidic impurities were observed. Using the Clinical Trials Network anthropomorphic chest phantom, SPECT/CT images were acquired. Medium energy (ME) SPECT collimation was found to provide the best image quality from the primary 185 keV gamma emission of 67Cu. Reconstructed images of 67Cu were similar in quality to images acquired using 177Lu. Recovery coefficients were calculated and compared against quantitative images of 99mTc, 177Lu, and 64Cu within the same anthropomorphic chest phantom. Production and clinical imaging of 67Cu appears feasible, and future studies investigating the therapeutic efficacy of 67Cu-based radiopharmaceuticals are warranted.

Accelerator Production of Scandium Radioisotopes: Sc-43, Sc-44, and Sc-47.

Scandium radioisotopes are increasingly considered viable radiolabels for targeted molecular imaging (Sc-43, Sc-44) and therapy (Sc-47). Significant technological advances have increased the quantity and quality of available radioscandium in the past decade, motivated in part by the chemical similarity of scandium to therapeutic radionuclides like Lu-177. The production and radiochemical isolation techniques applied to scandium radioisotopes are reviewed, focusing on charged particle and electron linac initiated reactions and using calcium and titanium as starting materials.

Electron linear accelerator production and purification of scandium-47 from titanium dioxide targets.

The photonuclear production of no-carrier-added (NCA) 47Sc from solid NatTiO2 and the subsequent chemical processing and purification have been developed. Scandium-47 was produced by the 48Ti(γ,p)47Sc reaction with Bremsstrahlung photons produced from the braking of electrons in a high-Z (W or Ta) convertor. Production yields were simulated with the PHITS code (Particle and Heavy Ion Transport-code System) and compared to experimental results. Irradiated TiO2 targets were dissolved in fuming H2SO4 in the presence of Na2SO4 and 47Sc was purified using the commercially available Eichrom DGA resin. Typical 47Sc recovery yields were >90% with excellent specific activity for small batches (<185 MBq batches).

Heavy ion linear accelerator for radiation damage studies of materials.

A new eXtreme MATerial (XMAT) research facility is being proposed at Argonne National Laboratory to enable rapid in situ mesoscale bulk analysis of ion radiation damage in advanced materials and nuclear fuels. This facility combines a new heavy-ion accelerator with the existing high-energy X-ray analysis capability of the Argonne Advanced Photon Source. The heavy-ion accelerator and target complex will enable experimenters to emulate the environment of a nuclear reactor making possible the study of fission fragment damage in materials. Material scientists will be able to use the measured material parameters to validate computer simulation codes and extrapolate the response of the material in a nuclear reactor environment. Utilizing a new heavy-ion accelerator will provide the appropriate energies and intensities to study these effects with beam intensities which allow experiments to run over hours or days instead of years. The XMAT facility will use a CW heavy-ion accelerator capable of providing beams of any stable isotope with adjustable energy up to 1.2 MeV/u for 238U50+ and 1.7 MeV for protons. This energy is crucial to the design since it well mimics fission fragments that provide the major portion of the damage in nuclear fuels. The energy also allows damage to be created far from the surface of the material allowing bulk radiation damage effects to be investigated. The XMAT ion linac includes an electron cyclotron resonance ion source, a normal-conducting radio-frequency quadrupole and four normal-conducting multi-gap quarter-wave resonators operating at 60.625 MHz. This paper presents the 3D multi-physics design and analysis of the accelerating structures and beam dynamics studies of the linac.